Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Schadler, P.
Knee osteoarthritis in the context of the metabolic syndrome
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2022. pp. 100
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Lohberger Birgit
- Steinecker-Frohnwieser Bibiane
- Stradner Martin Helmut
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- Abstract:
- Obesity and the metabolic syndrome are risk factors for and contribute to the pathogenesis of knee osteoarthritis (KOA). Diabetes in particular, a component of the metabolic syndrome, has been associated with disease progression. Metformin is the first-line treatment in type 2 diabetes mellitus. The connection of obesity and KOA remains unclear, but might be attributed to both mechanical loading and systemic low-grade inflammation. The relationship of BMI with and the effect of metformin stimulation on chondrocyte matrix gene expression is unknown. Furthermore, despite massive efforts over the past decades, no single diagnostic marker has been discovered that can reliably and accurately diagnose KOA. Finally, the relationship of BMI with cartilage thickness is controversial. The purpose of this thesis project was, first, to understand BMI-associated and metformin-induced changes in cartilage, as measured by the expression of extracellular matrix genes and the sonographic cartilage thickness. Second, to assess several metabolic biomarkers as diagnostic markers for the assessment of burden of disease (measured using the Lequesne index or sonographic cartilage thickness) and to evaluate their connection with obesity / the metabolic syndrome. To answer these questions we conducted 3 cross-sectional studies of adult patients undergoing knee arthroplasty. In three separate investigations, we assessed 1), the effect of metformin and BMI on matrix gene expression in primary, human chondrocytes, using polymerase chain reaction and multivariable regression analysis. 2) We measured serum levels of several metabolic biomarkers using the enzyme linked immunosorbent assay (ELISA) and the Luminex® technology. Furthermore we assessed the metabolic state using NMR spectroscopy, and examined their relationship with clinical KOA severity and obesity. 3) We measured serum biomarkers levels and examined their connection with sonographic cartilage thickness in the context of obesity. We found that obese patients had a higher expression rate of the degrading enzyme ADAMTS5, and this could be mitigated by metformin stimulation. We detected an association of cartilage thickness and BMI as well as the biomarker fatty acid-binding protein 4 (FABP4). We could not find an association of any biomarker with clinical KOA severity. This thesis project provided new insights to the relationship of obesity and KOA, identified FABP4 as promising new diagnostic blood biomarker, and explored the role of metformin as a possible therapeutic agent.